Despite improvements in the management of cardiovascular disease in type 2 diabetes, its prevalence remain still unacceptably high while numerous recent studies have indicated that improvements of glycemic control beyond a certain point have minimal, if any, effects on the macrovascular disease. This has led to the suggestion that targeting coexisting conditions, such as OSA, may be the new frontier in the effort to reduce risk of cardiovascular disease in diabetes. OSA was initially thought to be a marker of comorbidities related to an unfit lifestyle but is currently considered a real vascular risk factor. Thus, both animal and human epidemiological and interventional studies have shown that OSA can lead to development of cardiovascular disease. There is also a strong possibility that a synergistic interaction exists between OSA and diabetes significantly increasing cardiovascular risk, but before solid conclusions can be reached, the alternative hypothesis, namely that two diseases may offset one another or that risk may be limited by ceiling effects of the two diseases should be explored in more detail. The main hypothesis of the current application is that OSA and diabetes additively or synergistically increase the proinflammatory state that leads to endothelial dysfunction and the development of cardiovascular disease. We also hypothesize that appropriate treatment of OSA will improve vascular function in both the micro- and macrocirculation. Finally, we will test the hypothesis that this improvement is associated with a reduction of the proinflammatory state. In order to test our hypothesis, we will prospectively examine the effect of OSA treatment in the vascular function and the proinflammatory state of patients with DM and OSA. In order to test our hypothesis, the study will have three aims. The first aim will establish the combined effect of OSA and DM on cardiovascular function by comparing the effects of DM, OSA, and DM plus OSA on the ventricular function, aortic elasticity, vascular reactivity and proinflammatory status. The second aim involves a prospective, randomized clinical trial which will examine the effect of nasal continuous positive airway pressure (CPAP) treatment on the cardiovascular risk. The third aim will identify possible mechanisms through which OSA treatment reduces cardiovascular risk. The current proposal will encompass the collaboration of investigators working in various disciplines and has the potential to create very strong synergy and will lead to the generation of novel and very clinically useful data. Thus, it will be one of the very first ones in providing insight regarding the contributory effects of OSA in vascular disease in T2DM and the possible beneficial effects of OSA treatment. In that sense, it can have an immediate clinical effect as it may represent as paradigm shift in the way that OSA is viewed and managed by the professionals who treat T2DM patients. In addition, the proposed mechanistic studies have the potential to lead to new therapeutic approaches in the management of T2DM patients with OSA. PUBLIC HEALTH RELEVANCE: A strong synergistic interaction exists between OSA and diabetes significantly increasing cardiovascular risk, but before solid conclusions can be reached, the alternative hypothesis, namely that two diseases may offset one another or that risk may be limited by ceiling effects of the two diseases should be explored in more detail. We will establish the combined effect of OSA and DM on cardiovascular function by comparing the effects of DM, OSA, and DM plus OSA on the ventricular function, aortic elasticity, vascular reactivity and proinflammatory status. We will also investigate the effect of OSA treatment in the vascular function and the proinflammatory state of patients with DM and OSA.